Mixed Communities of Mucoid and Nonmucoid <italic toggle="yes">Pseudomonas aeruginosa</italic> Exhibit Enhanced Resistance to Host Antimicrobials

ABSTRACT Pseudomonas aeruginosa causes chronic pulmonary infections in patients with cystic fibrosis (CF). P. aeruginosa mucoid conversion, defined by overproduction of the exopolysaccharide alginate, correlates with accelerated decline in CF patient lung function. Recalcitrance of the mucoid phenot...

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Autores principales:	Sankalp Malhotra, Dominique H. Limoli, Anthony E. English, Matthew R. Parsek, Daniel J. Wozniak
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Pseudomonas aeruginosa alginate antimicrobial peptides catalase exopolysaccharide polymicrobial Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e7098af151384b5ea69a640e8d7bb4d6
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spelling	oai:doaj.org-article:e7098af151384b5ea69a640e8d7bb4d62021-11-15T15:53:26ZMixed Communities of Mucoid and Nonmucoid <italic toggle="yes">Pseudomonas aeruginosa</italic> Exhibit Enhanced Resistance to Host Antimicrobials10.1128/mBio.00275-182150-7511https://doaj.org/article/e7098af151384b5ea69a640e8d7bb4d62018-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00275-18https://doaj.org/toc/2150-7511ABSTRACT Pseudomonas aeruginosa causes chronic pulmonary infections in patients with cystic fibrosis (CF). P. aeruginosa mucoid conversion, defined by overproduction of the exopolysaccharide alginate, correlates with accelerated decline in CF patient lung function. Recalcitrance of the mucoid phenotype to clearance by antibiotics and the immune response is well documented. However, despite advantages conferred by mucoidy, mucoid variants often revert to a nonmucoid phenotype both in vitro and in vivo. Mixed populations of mucoid isolates and nonmucoid revertants are recovered from CF lungs, suggesting a selective benefit for coexistence of these variants. In this study, cocultures of mucoid and nonmucoid variants exhibited enhanced resistance to two host antimicrobials: LL-37, a cationic antimicrobial peptide, and hydrogen peroxide (H2O2). Alginate production by mucoid isolates protected nonmucoid variants in consortia from LL-37, as addition of alginate exogenously to nonmucoid variants abrogated LL-37 killing. Conversely, nonmucoid revertants shielded mucoid variants from H2O2 stress via catalase (KatA) production, which was transcriptionally repressed by AlgT and AlgR, central regulators of alginate biosynthesis. Furthermore, extracellular release of KatA by nonmucoid revertants was dependent on lys, encoding an endolysin implicated in autolysis and extracellular DNA (eDNA) release. Overall, these data provide a rationale to study interactions of P. aeruginosa mucoid and nonmucoid variants as contributors to evasion of innate immunity and persistence within the CF lung. IMPORTANCE P. aeruginosa mucoid conversion within lungs of cystic fibrosis (CF) patients is a hallmark of chronic infection and predictive of poor prognosis. The selective benefit of mixed populations of mucoid and nonmucoid variants, often isolated from chronically infected CF patients, has not been explored. Here, we show that mixed-variant communities of P. aeruginosa demonstrate advantages in evasion of innate antimicrobials via production of shared goods: alginate and catalase. These data argue for therapeutically targeting multiple constituents (both mucoid and nonmucoid variants) within diversified P. aeruginosa communities in vivo, as these variants can differentially shield one another from components of the host response.Sankalp MalhotraDominique H. LimoliAnthony E. EnglishMatthew R. ParsekDaniel J. WozniakAmerican Society for MicrobiologyarticlePseudomonas aeruginosaalginateantimicrobial peptidescatalaseexopolysaccharidepolymicrobialMicrobiologyQR1-502ENmBio, Vol 9, Iss 2 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pseudomonas aeruginosa alginate antimicrobial peptides catalase exopolysaccharide polymicrobial Microbiology QR1-502
spellingShingle	Pseudomonas aeruginosa alginate antimicrobial peptides catalase exopolysaccharide polymicrobial Microbiology QR1-502 Sankalp Malhotra Dominique H. Limoli Anthony E. English Matthew R. Parsek Daniel J. Wozniak Mixed Communities of Mucoid and Nonmucoid <italic toggle="yes">Pseudomonas aeruginosa</italic> Exhibit Enhanced Resistance to Host Antimicrobials
description	ABSTRACT Pseudomonas aeruginosa causes chronic pulmonary infections in patients with cystic fibrosis (CF). P. aeruginosa mucoid conversion, defined by overproduction of the exopolysaccharide alginate, correlates with accelerated decline in CF patient lung function. Recalcitrance of the mucoid phenotype to clearance by antibiotics and the immune response is well documented. However, despite advantages conferred by mucoidy, mucoid variants often revert to a nonmucoid phenotype both in vitro and in vivo. Mixed populations of mucoid isolates and nonmucoid revertants are recovered from CF lungs, suggesting a selective benefit for coexistence of these variants. In this study, cocultures of mucoid and nonmucoid variants exhibited enhanced resistance to two host antimicrobials: LL-37, a cationic antimicrobial peptide, and hydrogen peroxide (H2O2). Alginate production by mucoid isolates protected nonmucoid variants in consortia from LL-37, as addition of alginate exogenously to nonmucoid variants abrogated LL-37 killing. Conversely, nonmucoid revertants shielded mucoid variants from H2O2 stress via catalase (KatA) production, which was transcriptionally repressed by AlgT and AlgR, central regulators of alginate biosynthesis. Furthermore, extracellular release of KatA by nonmucoid revertants was dependent on lys, encoding an endolysin implicated in autolysis and extracellular DNA (eDNA) release. Overall, these data provide a rationale to study interactions of P. aeruginosa mucoid and nonmucoid variants as contributors to evasion of innate immunity and persistence within the CF lung. IMPORTANCE P. aeruginosa mucoid conversion within lungs of cystic fibrosis (CF) patients is a hallmark of chronic infection and predictive of poor prognosis. The selective benefit of mixed populations of mucoid and nonmucoid variants, often isolated from chronically infected CF patients, has not been explored. Here, we show that mixed-variant communities of P. aeruginosa demonstrate advantages in evasion of innate antimicrobials via production of shared goods: alginate and catalase. These data argue for therapeutically targeting multiple constituents (both mucoid and nonmucoid variants) within diversified P. aeruginosa communities in vivo, as these variants can differentially shield one another from components of the host response.
format	article
author	Sankalp Malhotra Dominique H. Limoli Anthony E. English Matthew R. Parsek Daniel J. Wozniak
author_facet	Sankalp Malhotra Dominique H. Limoli Anthony E. English Matthew R. Parsek Daniel J. Wozniak
author_sort	Sankalp Malhotra
title	Mixed Communities of Mucoid and Nonmucoid <italic toggle="yes">Pseudomonas aeruginosa</italic> Exhibit Enhanced Resistance to Host Antimicrobials
title_short	Mixed Communities of Mucoid and Nonmucoid <italic toggle="yes">Pseudomonas aeruginosa</italic> Exhibit Enhanced Resistance to Host Antimicrobials
title_full	Mixed Communities of Mucoid and Nonmucoid <italic toggle="yes">Pseudomonas aeruginosa</italic> Exhibit Enhanced Resistance to Host Antimicrobials
title_fullStr	Mixed Communities of Mucoid and Nonmucoid <italic toggle="yes">Pseudomonas aeruginosa</italic> Exhibit Enhanced Resistance to Host Antimicrobials
title_full_unstemmed	Mixed Communities of Mucoid and Nonmucoid <italic toggle="yes">Pseudomonas aeruginosa</italic> Exhibit Enhanced Resistance to Host Antimicrobials
title_sort	mixed communities of mucoid and nonmucoid <italic toggle="yes">pseudomonas aeruginosa</italic> exhibit enhanced resistance to host antimicrobials
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/e7098af151384b5ea69a640e8d7bb4d6
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Mixed Communities of Mucoid and Nonmucoid <italic toggle="yes">Pseudomonas aeruginosa</italic> Exhibit Enhanced Resistance to Host Antimicrobials

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